Cluster analysis of sputum cytokine-high profiles reveals diversity in T(h)2-high asthma patients.

ABSTRACT: Asthma is characterized by a heterogeneous inflammatory profile and can be subdivided into T(h)2-high and T(h)2-low airway inflammation. Profiling of a broader panel of airway cytokines in large unselected patient cohorts is lacking.Patients (n?=?205) were defined as being "cytokine-low/high" if sputum mRNA expression of a particular cytokine was outside the respective 10th/90th percentile range of the control group (n?=?80). Unsupervised hierarchical clustering was used to determine clusters based on sputum cytokine profiles.Half of patients (n?=?108; 52.6%) had a classical T(h)2-high ("IL-4-, IL-5- and/or IL-13-high") sputum cytokine profile. Unsupervised cluster analysis revealed 5 clusters. Patients with an "IL-4- and/or IL-13-high" pattern surprisingly did not cluster but were equally distributed among the 5 clusters. Patients with an "IL-5-, IL-17A-/F- and IL-25- high" profile were restricted to cluster 1 (n?=?24) with increased sputum eosinophil as well as neutrophil counts and poor lung function parameters at baseline and 2 years later. Four other clusters were identified: "IL-5-high or IL-10-high" (n?=?16), "IL-6-high" (n?=?8), "IL-22-high" (n?=?25). Cluster 5 (n?=?132) consists of patients without "cytokine-high" pattern or patients with only high IL-4 and/or IL-13.We identified 5 unique asthma molecular phenotypes by biological clustering. Type 2 cytokines cluster with non-type 2 cytokines in 4 out of 5 clusters. Unsupervised analysis thus not supports a priori type 2 versus non-type 2 molecular phenotypes. www.clinicaltrials.gov NCT01224938. Registered 18 October 2010.

SUBMITTER: Seys SF 

PROVIDER: S-EPMC5324270 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature